Pyridine → HCID 71584706, compound

HRID 1430531Notes

Reaction equation

HRID 1430531 reaction equation
CS(O)(=O)=O.[NH2:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:20]3[C:21]([Cl:37])=[CH:22][C:23]([F:36])=[C:24]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:28])[CH:25]=3)[C:13](=[O:19])[N:14]2[CH2:17][CH3:18])=[CH:9][N:8]=1.N1C=CC=CC=1.[CH3:44][O:45][CH2:46][C:47](Cl)=[O:48].CCOC(C)=O>C1COCC1.O>[Cl:37][C:21]1[CH:22]=[C:23]([F:36])[C:24]([NH:26][C:27]([NH:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:28])=[CH:25][C:20]=1[C:12]1[C:13](=[O:19])[N:14]([CH2:17][CH3:18])[C:15]2[C:10]([CH:11]=1)=[CH:9][N:8]=[C:7]([NH:6][C:47](=[O:48])[CH2:46][O:45][CH3:44])[CH:16]=2

Participants

7

Reactant 4

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 96623Methoxyacetyl chloride2×HCID 86713641HCID 86713641, compound

Product 1

HCID 71584706HCID 71584706, compoundYield 72.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of Example 21 (90 mg, 0.199 mmol) and pyridine (79 mg, 0.996 mmol) in THF (4 mL) was treated drop-wise with methoxy acetyl chloride (27 mg, 0.249 mmol) and stirred at RT for 22 h. Additional methoxy acetyl chloride (30 μL, 0.328 mmol) was added, the mixture heated at 40° C. for 6 h, then cooled to RT and stirred overnight. The mixture was treated with EtOAc and water, stirred for 1 h, the resulting solid collected via filtration and dried to afford N-(3-(2-chloro-4-fluoro-5-(3-phenylureido)phenyl)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)-2-methoxyacetamide (76 mg, 72% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.39 (s, 1H), 9.09 (s, 1H), 8.73 (m, 2H), 8.27-8.20 (m, 2H), 8.00 (s, 1H), 7.58 (d, J=10.9 Hz, 1H), 7.41 (d, J=8.0 Hz, 2H), 7.26 (t, J=7.7 Hz, 2H), 6.97 (t, J=7.3 Hz, 1H), 4.21 (q, J=7.1 Hz, 2H), 4.12 (s, 2H), 3.38 (s, 3H), 1.26 (t, J=7.1 Hz, 3H); MS (ESI) m/z: 524.2 [M+H]+.

Workup

  1. temperaturethe mixture heated at 40° C. for 6 h
  2. temperaturecooled to RT
  3. stirringstirred overnight
  4. stirringstirred for 1 h
  5. filtrationthe resulting solid collected via filtration
  6. customdried

Sources & evidence

ORD record
ord-9d58796950574b4c9ef15af6739f984b
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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